Pharmacologic Prevention of Incident Atrial Fibrillation: Long-Term Results From the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial)

Abstract

Background: Although atrial fibrillation (AF) guidelines indicate that pharmacological blockade of the renin-angiotensin system may be considered for primary AF prevention in hypertensive patients, previous studies have yielded conflicting results. We sought to determine whether randomization to lisinopril reduces incident AF or atrial flutter (AFL) compared with chlorthalidone in a large clinical trial cohort with extended post-trial surveillance.

Methods and results: We performed a secondary analysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), a randomized, double-blind, active-controlled clinical trial that enrolled hypertensive individuals ≥55 years of age with at least one other cardiovascular risk factor. Participants were randomly assigned to receive amlodipine, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin versus usual care. The primary outcome was the development of either AF or AFL as diagnosed by serial study ECGs or by Medicare claims data. Among 14 837 participants without prevalent AF or AFL, 2514 developed AF/AFL during a mean 7.5±3.2 years of follow-up. Compared with chlorthalidone, randomization to either lisinopril (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15; P=0.46) or amlodipine (hazard ratio, 0.93; 95% confidence interval, 0.84-1.03; P=0.16) was not associated with a significant reduction in incident AF/AFL.

Conclusions: Compared with chlorthalidone, treatment with lisinopril is not associated with a meaningful reduction in incident AF or AFL among older adults with a history of hypertension.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Keywords: antihypertensive agents; atrial fibrillation; atrial flutter; primary prevention; renin-angiotensin system.

Figure 1

Selection of Study Participants from the Overall ALLHAT Cohort AF, atrial fibrillation; AFL, atrial flutter; CMS, Centers for Medicare Services; ECG, electrocardiogram.

Figure 2

Multivariable Predictors of Incident Atrial Fibrillation or Flutter *Per 5 year increase in age. †Compared to White non-Hispanics. ‡Per 5 kg/m² increase. §Per 10 ml/min/1.73 m² increase. ||Per mEq/L increase. #Per 10mg/dl increase. Error bars denote 95% confidence intervals. Hazard ratios describe the adjusted association between the given variable and AF/AFL after controlling for all clinical variables included in the Figure, antihypertensive treatment assignment, and statin treatment assignment. CI, confidence interval; GFR, glomerular filtration rate; HR, hazard ratio.

Figure 3

ALLHAT Treatment Randomization and Incident Atrial Fibrillation or Flutter *Compared to chlorthalidone. †Compared to usual care. Error bars denote 95% confidence intervals. Adjusted hazard ratios describe the adjusted association between treatment randomization and incident atrial fibrillation or flutter after adjustment for all clinical variables included in Table 1. CI, confidence interval; HR, hazard ratio.